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Introduction MEK inhibition is a potential therapeutic strategy in non-small cell lung cancer (NSCLC). This phase I study evaluates the MEK inhibitor binimetinib plus carboplatin and pemetrexed in stage IV non-squamous NSCLC patients (NCT02185690). Methods A standard 3 + 3 dose-escalation design was used. Binimetinib 30 mg BID (dose level 1 [DL1]) or 45 mg BID (dose level 2 [DL2]) was given with standard doses of carboplatin and pemetrexed using an intermittent dosing schedule. The primary outcome was determination of the recommended phase II dose (RP2D) and safety of binimetinib. Secondary outcomes included efficacy, pharmacokinetics, and an exploratory analysis of response based on mutation subtype. Results Thirteen patients (6 DL1, 7 DL2) were enrolled: 7 KRAS, 5 EGFR, and 1 NRAS mutation. The RP2D was binimetinib 30 mg BID. Eight patients (61.5%) had grade 3/4 adverse events, with dose limiting toxicities in 2 patients at DL2. Twelve patients were evaluated for response, with an investigator-assessed objective response rate (ORR) of 50% (95% CI 21.1%-78.9%; ORR 33.3% by independent-review, IR), and disease control rate 83.3% (95% CI 51.6%-97.9%). Median progression free survival (PFS) was 4.5 months (95% CI 2.6 months–NA), with a 6-month and 12-month PFS rate of 38.5% (95% CI 19.3%-76.5%) and 25.6% (95% CI 8.9%-73.6%), respectively. In an exploratory analysis, KRAS/NRAS-mutated patients had an ORR of 62.5% (ORR 37.5% by IR) vs. 25% in KRAS/NRAS wild-type patients. In MAP2K1–mutated patients, the ORR was 42.8%. Conclusion The addition of binimetinib to carboplatin and pemetrexed appears to have manageable toxicity with evidence of activity in advanced non-squamous NSCLC.

BACKGROUND AND OBJECTIVE: Long-term electrocardiogram monitoring comes at the expense of signal quality. During unconstrained movements, the electrocardiogram is often corrupted by motion artefacts, which can lead to inaccurate physiological information. In this situation, automated quality assessment methods are useful to increase the reliability of the measurements. A generic machine learning pipeline that generates classification models for electrocardiogram quality assessment is presented in this article. The presented pipeline is tested on signals from varied acquisition sources, towards selecting segments that can be used for heart rate analysis in lifestyle applications. METHODS: Electrocardiogram recordings from traditional, wearable and ubiquitous devices, are segmented in 10 s windows and manually labeled by experienced researchers into two quality classes. To capture the electrocardiogram dynamics, a comprehensive set of 43 features is extracted from each segment, based on the time-domain signal, its Fast Fourier Transform, the Autocorrelation function and the Stationary Wavelet Transform. To select the most relevant features for each acquisition source we employ both a customized hybrid approach and the state-of-the-art Neighborhood Component Analysis method and compare them. Support Vector Machines (SVM), Decision Trees, K-Nearest-Neighbors and supervised ensemble methods are tested as possible binary classifiers. RESULTS: The results for the best performing models on traditional, wearable and ubiquitous electrocardiogram datasets are, respectively: balanced-accuracy: 89%, F1-score: 93% with the Fine Gaussian SVM model and 10 features; balanced-accuracy: 93%, F1-score: 93% with the Fine Gaussian SVM model and 11 features; balanced-accuracy: 95%, F1-score: 86%, with the Fine Gaussian SVM model and 8 features. CONCLUSIONS: According to the results, our generic pipeline can generate classification models tailored to individual acquisition sources, provided that a standard Lead I or Lead II is available. Such models accurately establish whether the electrocardiogram quality is good or bad for heart rate analysis. Furthermore, removing bad quality segments decreases errors in heart rate calculation. ispartof: COMPUTERS IN BIOLOGY AND MEDICINE vol:130 ispartof: location:United States status: published

With advances in genetic testing and improved access to such advances, whole exome sequencing is becoming a first-line investigation in clinical work-up of children with developmental delay/intellectual disability (ID). As a result, the need to understand the importance of genetic variants and its effect on the clinical phenotype is increasing. Here, we report on the largest cohort of patients with HNRNPU variants. These 21 patients follow on from the previous study published by Yates et al. in 2017 from our group predominantly identified from the Deciphering Developmental Disorders study that reported seven patients with HNRNPU variants. All the probands reported here have a de novo loss-of-function variant. These probands have craniofacial dysmorphic features, in the majority including widely spaced teeth, microcephaly, high arched eyebrows, and palpebral fissure abnormalities. Many of the patients in the group also have moderate to severe ID and seizures that tend to start in early childhood. This series has allowed us to define a novel neurodevelopmental syndrome, with a likely mechanism of haploinsufficiency, and expand substantially on already published literature on HNRNPU-related neurodevelopmental syndrome.

Introduction This study was performed to evaluate the clinical efficacy of using the Perio-Flow device (Electro Medical Systems, Nyon, Switzerland) adjunctively with mechanical instrumentation on periodontal parameters and halitosis. Materials and Methods Sixty patients who presented with a 4- to 6-mm probing pocket depth were recruited for the study. Patients were randomly assigned to scaling and root planing (SRP) or SRP + glycine powder air-polishing (GPAP). For both groups, the plaque index, gingival index, pocket depth, bleeding on probing, and clinical attachment level scores were recorded at baseline and 1 month. Volatile sulphur compounds (VSCs) were measured by a Halimeter (Interscan Corp., Chatsworth, CA, USA) at baseline, immediately after treatment, and at 7, 14, and 30 days. Results Both groups showed significantly lower plaque index, gingival index, pocket depth, bleeding on probing, and clinical attachment level gain scores at 1 month than at baseline. No significant differences were found between the groups at any time point. The VSCs were significantly different at 1 month compared with baseline in both groups. However, the intergroup comparisons of VSCs were not statistically significant at any time point. Conclusion Within the limits of this study, SRP is effective for treatment of periodontitis and halitosis. However, using GPAP adjunctively with mechanical instrumentation has no beneficial effects on halitosis or periodontal parameters.

Three hundred eleven honeybee samples from twelve countries in the Middle East and North Africa (MENA) (Jordan, Lebanon, Syria, Iraq, Egypt, Libya, Tunisia, Algeria, Morocco, Yemen, Palestine and Sudan) were analyzed for the presence of deformed wing virus (DWV). The prevalence of DWV throughout the MENA region was pervasive, but variable. The highest prevalence was found in Lebanon and Syria, with prevalence dropping in Palestine, Jordan and Egypt before increasing slightly moving westwards to Algeria and Morocco Phylogenetic analysis of a 194 nucleotide section of the DWV Lp gene did not identify any significant phylogenetic resolution among the samples, although the sequences did show consistent regional clustering, including an interesting geographic gradient from Morocco through North Africa to Jordan and Syria. The sequences revealed several clear variability hotspots in the deduced amino acid sequence, that furthermore showed some patterns of regional identity. Furthermore, the sequence variants from the Middle East and North Africa appear more numerous and diverse than those from Europe. This article is protected by copyright. All rights reserved.

Monoclonal antibodies targeting programmed cell death protein-1 (PD-1) represent a new treatment paradigm in non-small cell lung cancer. Three phase III trials have demonstrated a survival benefit and improved tolerability of nivolumab and pembrolizumab when compared with standard second-line chemotherapy. Nevertheless, the adverse events associated with PD-1 inhibitors are unique; early recognition and treatment are essential. This review summarizes the required monitoring and appropriate management of immune-related adverse events in lung cancer patients receiving these agents. THE ONCOLOGIST 2017;22:70-80 IMPLICATIONS FOR PRACTICE: : The potential adverse events of immune checkpoint inhibitors differ from conventional chemotherapy and can require a multidisciplinary approach. Continued education is important for all physicians to ensure optimal care for patients.